Specific interaction of the new fluorescent dye 10-N-nonyl acridine orange with inner mitochondrial membrane. A lipid-mediated inhibition of oxidative phosphorylation.
The fluorescent dye 10-N-nonyl acridine orange (NAO), known as specifically associated with mitochondria, has been reported to have a cytotoxic effect when high doses were applied to cells. Presently, the biochemical basis of its toxicity was investigated on isolated rat liver mitochondria. At low concentrations, NAO strongly inhibited state 3 respiration and ATP synthesis. At high concentrations, electron transport, ATP hydrolysis, Pi-transport and adenine nucleotide activities were also decreased. All these inhibitions can be explained by probe-cardiolipin interactions which could induce the collapse of energy conversion and/or the modification of membrane fluidity.
Maftah
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Genius (Unité de Biotechnologie), Faculté des Sciences, Limoges, France.
Petit
J M
JM
Julien
R
R
D000165:Acridine Orange / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D004579:Electron Transport / Q000187:drug effects; D008055:Lipids / Q000502:physiology; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D000226:Mitochondrial ADP, ATP Translocases / Q000037:antagonists & inhibitors; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010710:Phosphates / Q000378:metabolism; D051381:Rats
D008055:Lipids; D010710:Phosphates; D000255:Adenosine Triphosphate; D000226:Mitochondrial ADP, ATP Translocases; D000165:Acridine Orange